A particular class of aminopentane derivatives have already been described as having a catecholaminergic activity enhancing effect (CAE effect) by enhancing membrane potential dependent exocytosis, which effect differs from that of monoamine oxidase inhibitors, catecholamine uptake inhibitors or catecholamine substitution type release stimulating agents (for example, see Patent Literature 1 listed below). In particular they have been described to be devoid of excessive catecholamine release or amine depletion at catecholamine nerve terminals, which are observed with catecholamine substitution type release stimulating agents.
Such aminopentane derivatives are expected to have fewer side effects such as abnormal hyperactivity (excitatory effect) and neurotoxicity in the central nervous system, to have fewer problems such as decreasing responsiveness of patients, and to be highly effective as a safe and useful antidepressant, psychotropic, antiparkinsonian, or anti-Alzheimer's agents. It has also been reported that the aminopentane derivatives have an asymmetric carbon in the molecular structure and optically active isomers of them were found to be more effective than racemates (for example, see Patent Literature 2 and Non-Patent Literature 1 listed below).
Concerning 1-(benzofuran-2-yl)-2-propylaminopentane, for example, the (−) form with the R configuration has a higher pharmacological activity as compared with the (+) form with the S configuration or the racemate (see Patent Literature 2 and Non-Patent Literature 1). In addition, it is disclosed that the (R)-1-(benzofuran-2-yl)-2-propylaminopentane has an anti-apoptosis activity and is potentially useful as an apoptosis inhibitor against Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, retinitis pigmentosa, glaucoma, nervous diseases such as spinocerebellar degeneration, ischemic brain diseases such as stroke, neurodegenerative diseases such as peripheral nerve disorder observed in diabetes, AIDS, and toxic diseases (for example, see Patent Literature 3 listed below).
Conventionally known process for preparing optically active aminopentane derivatives such as (R)-1-(benzofuran-2-yl)-2-propylaminopentane comprises a synthesis of the racemates from various aromatic aldehydes via nitroalkene intermediates followed by their optical resolution. However, such processes require not only an equivalent amount or more of a reagent, such as an optically active acid, to the amine but also troublesome operation such as crystallization, separation and purification. For example, optically active (R)-1-(benzofuran-2-yl)-2-propylaminopentane could not be obtained from a synthesized racemate by an optical resolution via formation of diastereomeric salts or derivatives but could only be separated by preparative high-performance liquid chromatography using a chiral column. Such separation requires a large amount of solvent and a lot of time and is a less productive method by which only at most about 50% of the desired optically active substance can be recovered (see Patent Literatures 1 and 2). Other methods using enzymes and some asymmetric synthesis methods are also known and they might be applicable to a preparation of the aminopentanes, however, these methods are less practical in view of limited substrates, insufficient selectivity and complicated operation.
Thus, there have been developed two different practical processes for preparing optically active 1-(benzofuran-2-yl)-2-propylaminopentane. The first process comprises treating an optically active aziridine derivative prepared from an optically active norvaline with 2-benzofuran lithium to build up a framework of the optically active 1-(benzofuran-2-yl)-2-propylaminopentane. The second process comprises treating an optically active N-methoxy-N-methylamide derivative prepared from an optically active norvaline with 2-benzofuran lithium to obtain a ketone and reducing the ketone to build up a framework of the optically active 1-(benzofuran-2-yl)-2-propylaminopentane. The development of these two processes allows efficient production of both optically active isomers of 1-(benzofuran-2-yl)-2-propylaminopentane (see Patent Literature 4 listed below). However, research and development has been carried out in order to seek more industrially advantageous processes than these processes.
Patent Literature 1: Pamphlet of International Publication No. WO99/07667
Patent Literature 2: Japanese Patent Application Laid-Open (JP-A) No. 2000-136187
Patent Literature 3: JP-A No. 2003-89643
Patent Literature 4: Pamphlet of International Publication No. WO01/77074
Non-Patent Literature 1: Yoneda et al., Bioorganic & Medicinal Chemistry, 2001 Vol. 9, pp. 1197-1212